CCR5 is involved in resolution of inflammation in proteoglycan‐induced arthritis

Abstract

Objective CCR5 and its ligands (CCL3, CCL4, and CCL5) may play a role in inflammatory cell recruitment into the joint. However, it was recently reported that CCR5 on T cells and neutrophils acts as a decoy receptor for CCL3 and CCL5 to assist in the resolution of inflammation. The aim of this study was to determine whether CCR5 functions as a proinflammatory or antiinflammatory mediator in arthritis, by examining the role of CCR5 in proteoglycan (PG)–induced arthritis (PGIA). Methods Arthritis was induced by immunizing wild‐type (WT) and CCR5‐deficient (CCR5^−/−) BALB/c mice with human PG in adjuvant. The onset and severity of PGIA were monitored over time. Met‐RANTES was used to block CCR5 in vivo. Arthritis was transferred to SCID mice, using spleen cells from arthritic WT and CCR5^−/− mice. The expression of cytokines and chemokines was measured by enzyme‐linked immunosorbent assay. Results In CCR5^−/− mice and WT mice treated with the CCR5 inhibitor Met‐RANTES, exacerbated arthritis developed late in the disease course. The increase in arthritis severity in CCR5^−/− mice correlated with elevated serum levels of CCL5. However, exacerbated arthritis was not intrinsic to the CCR5^−/− lymphoid cells, because the arthritis that developed in SCID mouse recipients was similar to that in WT and CCR5^−/− mice. CCR5 expression in the SCID mouse was sufficient to clear CCL5, because serum levels of CCL5 were the same in SCID mouse recipients receiving cells from either WT or CCR5^−/− mice. Conclusion These data demonstrate that CCR5 is a key player in controlling the resolution of inflammation in experimental arthritis.